4.6 Article

Ustekinumab reduces serum protein levels associated with cardiovascular risk in psoriasis vulgaris

Journal

EXPERIMENTAL DERMATOLOGY
Volume 31, Issue 9, Pages 1341-1351

Publisher

WILEY
DOI: 10.1111/exd.14582

Keywords

biologic; biomarker; blood; inflammatory; interleukin-6

Categories

Funding

  1. American Heart Association Career Development Grant [18CDA34080540]
  2. National Psoriasis Foundation Bridge Grant
  3. K23 Career Development Award [K23 HL152013]

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This study aimed to identify biomarkers of cardiovascular (CV) risk in psoriasis blood that are reduced by ustekinumab. The results showed that 43 out of 276 proteins were down-regulated after treatment, and 8 of them were initially elevated above thresholds associated with enhanced CV risk.
Psoriasis increases the risk of cardiovascular disease (CVD). Biomarkers for cardiovascular (CV) risk stratification in psoriasis are lacking, and the effects of psoriasis biologics on CV risk reduction remain unclear. The goal of this study was to identify biomarkers of CV risk in psoriasis blood that are reduced by ustekinumab. We quantified 276 inflammatory and CV-related serum proteins with Olink's multiplex assay in 10 psoriasis patients (vs. 18 healthy controls) and after 12 weeks of ustekinumab treatment. For each protein down-regulated after treatment, the literature was reviewed for studies assessing the protein's association with CVD. Data were collected from each study to calculate CV risk thresholds for each protein, which were compared with protein levels in psoriasis patients before and after treatment. Our results showed that 43 out of 276 proteins were down-regulated after treatment, 25 of which were initially up-regulated at baseline (vs. controls, all p-values <= 0.1). 8 down-regulated proteins were initially elevated above thresholds associated with enhanced CV risk in the literature (myeloperoxidase, C-X-C motif chemokine 10, E-selectin, interleukin-6, cystatin B, von Willebrand factor, tumor necrosis factor receptor 1 and N-terminal prohormone brain natriuretic peptide). Treatment lowered these proteins to below their risk thresholds, except for IL-6, which was lowered but remained at its risk threshold despite successful psoriasis skin treatment. In summary, 12 weeks of ustekinumab treatment reduced serum proteins present at levels associated with CV risk in psoriasis patients. Further studies can evaluate these proteins as potential ustekinumab-modulated biomarkers of CV risk in psoriasis and the impact of ustekinumab on CV risk reduction.

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